Alkylated aromatic compounds, in particular, a group of aromatic compounds having a secondary alkyl group on the aromatic ring are known to be useful as intermediates for chemical products including medical drugs, agricultural chemicals, etc., as raw materials for liquid crystals, and so on.
As a process for site-selective production of aromatic compounds having a secondary alkyl group, a coupling reaction of alkyl magnesium reagents with aryl halides or aryl sulfonates in the presence of a nickel or palladium catalyst was hitherto known (Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.; Hirotsu, K.; J. Am. Chem. Soc. 1984, 106, 158-163, Ogasawara, M.; Yoshida, K.; Hayashi, T.; Organometallics, 2000, 19, 1567-1571, Doherty, S.; Knight, J.; Robins, E. G.; Scanlan, T. H.; Champkin, P. A. Clegg, W.; J. Am. Chem. Soc. 2001, 123, 5110-5111).
However, this process essentially requires addition of a phosphine ligand having a complicated structure and is further accompanied by isomerization of the secondary alkyl group into a primary alkyl group, depending upon structure of the secondary alkyl group, which results in a problem that the objective product cannot be obtained in a high yield. Another problem is that highly toxic or expensive catalysts such as a nickel catalyst or a palladium catalyst are required and hence, the process cannot be applied to mass production in the fields of medical drugs or agricultural chemicals where use of highly toxic reagents should be avoided.
As processes for producing aromatic compounds having alkyl groups from alkyl halides or alkyl sulfonates and aromatic organometallic reagents, a cross-coupling of alkyl sulfonates or alkyl halides with aromatic magnesium reagents in the presence of a diene ligand using palladium as a catalyst (Terao, J.; Naitoh, Y.; Kuniyasu, H.; Kambe, N.; Chem. Lett. 2003, 32, 890-901) and a process for catalytic cross-coupling of alkyl halides with aromatic magnesium reagents in the presence of a diene ligand using copper or nickel as a catalyst are also known (Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N.; J. Am. Chem. Soc. 2003, 125, 5646-5647).
In addition, a palladium-catalyzed cross-coupling reaction of alkyl halides with aromatic zinc compounds, aromatic tin compounds or aromatic silicon compounds in the presence of a bulky phosphine ligand such as tricyclohexylphosphin is also known (Zhou, J.; Fu, G. C.; J. Am. Chem. Soc. 2003, 125, 12527-12530, Tang, H.; Menzel, K.; Fu, G. C.; Angew. Chem., Int. Ed. 2003, 42, 5079-5082, Lee, J.-Y.; Fu, G. C.; J. Am. Chem. Soc. 2003, 125, 5616-5617).
In the case of introducing a secondary alkyl group by these processes, however, alkenes are produced by side-reactions such as an elimination reaction to give the objective product only in a poor yield, and these processes involve a problem that they are not available for synthesis of aromatic compounds having a secondary alkyl substituent(s).
As a process for producing aromatic compounds having an alkyl group from secondary alkyl halides and aromatic organometallic compounds, there is also known a process which comprises catalytic cross-coupling of aromatic boron compounds with secondary alkyl halides using a nickel catalyst (Zhou, J.; Fu, G. C.; J. Am. Chem. Soc. 2004, 126, 1340-1341). In this process, aromatic compounds having various secondary alkyl substituents can be synthesized but the problem that highly toxic nickel should be used still remains unsolved.
Also, a cross-coupling reaction of an unsaturated organic halide such as an aryl halide or alkenyl halide or an electrophilic reagent such as allyl phosphate, etc. with an aromatic or alkyl magnesium reagent, a zinc reagent or a manganese reagent is known as a process using an inexpensive and low-toxic iron catalyst as a catalyst (Fürstner, A.; Leitner; A. Angew. Chem., Int. Ed. 2002, 41, 609-612, Fürstner, A.; Leitner, A.; Mendez, M.; Krause, H.; J. Am. Chem. Soc. 2002, 124, 13856-13863, Pre-Grant patent Publication No. 2003/0220498).
According to this process, it is possible to synthesize an aromatic compound having a secondary alkyl substituent from a secondary alkyl magnesium reagent and an aryl halide. However, the process involves such disadvantages that many functional groups including carbonyl, cyano, etc. cannot be present concurrently upon preparation of the secondary alkyl magnesium reagent. Moreover, the yield is as low as 50%-60%, which is unsuited for a process for producing a variety of alkylated aromatic compounds. Further when an alkyl halide and an aromatic magnesium reagent are used under the reaction conditions of this process, olefins are predominantly formed by side reactions such as elimination, etc., and the process is disadvantageous in that the objective product is produced only in a poor yield.
A process which comprises a coupling reaction of an alkyl halide with an aromatic magnesium reagent using an iron complex catalyst having a catalytic amount of N,N,N′,N′-tetramethylethylenediamine (TMEDA) as a ligand is also known (Martin, R.: Fürstner, A.; Angew. Chem., Int. Ed. 2004, 43, 3955-3957). According to this process, however, there was a problem that the reaction did not proceed at all when the chloride or fluoride was used as the alkyl halide.
Moreover, a process which involves coupling as in the process described above, except for using a trivalent iron acetylacetonate complex as the catalyst, using no diamine ligand and changing the solvent from tetrahydrofuran (THF) to diethyl ether, is also known (Nagano, T.; Hayashi, T.; Org. Lett. 2004, 6, 1297-1299). However, this process was also disadvantageous in that the reaction did not proceed at all when the chloride or fluoride was used as the alkyl halide. In addition, the process involved another problem that the yield is generally poor and not practical.
It would be desired to provide a highly safe process capable of mass production, which can produce aromatic compounds having a variety of primary or secondary alkyl substituents in a high yield.